HER2+ Advanced Breast CancerPhase 1/2NCT06027983
Chimeric Receptor T Cells With Trastuzumab in HER2+ Advanced Breast Cancer and Other Solid Tumors
A Phase 1/2 study testing Chimeric receptor T-cells + Trastuzumab and Fludarabine and Cyclophosphosphamide in people with HER2+ Advanced Breast Cancer and Other Solid Tumors, run by National University Hospital, Singapore.
Trial summary
This phase Ib study aims to assess the safety and feasibility of combination of chimeric receptor T cells with trastuzumab in patients with HER2+ solid tumors, with further expansion of study population in HER2+ metastatic breast cancer once safety has been established. Read more about this study
- Who is it for?
- Ages 21 to 99 years
- Conditions the study is for
- HER2+ Advanced Breast Cancer, Other Solid Tumors
- What is being tested?
- Chimeric receptor T-cells + Trastuzumab and Fludarabine and Cyclophosphosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- No sites listed yet
- Study dates
- 1 Nov 2026to 31 Dec 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients may be included in the study only if they meet all of the following criteria:
- Age ≥ 21 years.
- Histologically confirmed diagnosis of HER2-positive cancer defined by immunohistochemistry (IHC) to be HER2 IHC3+ or HER2 IHC2+ and FISH positive. If immunohistochemistry is not available, FISH method is acceptable. The HER2 positivities by FISH is determined as FISH amplification ratio positive by institutional guidelines. Tumor subtype for each phase include :
- Phase I: HER2-positive breast or gastric cancer or other treatment-refractory HER2-positive solid tumors
- Phase II : HER2-positive breast carcinoma
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
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- Has measurable or evaluable disease based on RECIST 1.1 criteria
- Estimated life expectancy of at least 12 weeks.
- Prior lines of therapy:
- HER2-positive breast cancer - patient must have failed at least two lines of anti-HER2 based therapy for advanced/metastatic cancer. Patients with documented relapse while receiving or within 6 months of completion of adjuvant or neoadjuvant trastuzumab for HER2-positive breast cancer will be considered as 1 prior line of therapy.
- HER2-positive gastric cancer - patient must have failed at least one line of anti-HER2 based therapy.
- Other refractory HER2-positive solid tumors (non-breast, non-gastric) - have no standard therapies or have failed or unable to tolerate standard therapies
- Has recovered from acute toxicities from prior anti-cancer therapies
- Left ventricular ejection fraction ≥50%
- Adequate organ function including the following:
- o Bone marrow: Absolute neutrophil (segmented and bands) count (ANC) ≥ 1.5 x 109/L Platelets ≥ 100 x 109/L Haemoglobin ≥ 8 x 109/L
- o Hepatic: Bilirubin ≤ 1.5 x upper limit of normal (ULN), ALT or AST≤ 2.5x ULN, (or ≤5 X with liver metastases)
- o Renal: Creatinine ≤ 1.5x ULN
- Signed informed consent from patient or legal representative.
- Able to comply with study-related procedures.
- Specific to cohorts 3, 4 and 5 : Patients who have a history of VTE are eligible if as long as they are receiving therapeutic/prophylactic doses of anticoagulation.
Who cannot join
- Patients will be excluded from the study for any of the following reasons:
- Treatment within the last 30 days with any investigational drug.
- Concurrent administration of any other tumour therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy.
- Major surgery within 28 days of study drug administration.
- Active infection that in the opinion of the investigator would compromise the patient's ability to tolerate therapy.
- Pregnancy.
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- Breast feeding.
- Serious concomitant disorders that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator.
- Active bleeding disorder or bleeding site.
- Non-healing wound.
- Poorly controlled diabetes mellitus.
- Second primary malignancy that is clinically detectable at the time of consideration for study enrolment.
- Symptomatic brain metastasis.
- History of significant neurological or mental disorder, including seizures or dementia,
- History of autoimmune disease or use of gamma immunoglobulin
- Unable to comply with study procedures
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Phase IB Followed by Phase II Study of Trastuzumab Combined With Autologous Chimeric Receptor T Cells in HER2+ Advanced Breast Cancer and Other Solid Tumors
This phase Ib study aims to assess the safety and feasibility of combination of chimeric receptor T cells with trastuzumab in patients with HER2+ solid tumors, with further expansion of study population in HER2+ metastatic breast cancer once safety has been established.
Read the detailed description
Hypothesis
Investigators hypothesize that trastuzumab-mediated cytotoxicity will be augmented by the infusion of autologous chimeric receptor T-cells.
Primary Objectives
- To determine the safety of autologous chimeric receptor T-cells in patients with HER2+ advanced solid tumors
- To determine the clinical benefit rate (CBR) of autologous chimeric receptor T-cells in patients with HER2+ advanced breast cancer
Secondary Objectives
- To determine the expansion and persistence of autologous chimeric receptor T-cells after a single infusion in patients with advanced solid tumors
- To determine anti-tumor efficacy in terms of objective response rate (ORR) and progression-free survival (PFS) of autologous chimeric receptor T-cells in patients with HER2+ advanced breast cancer
- Conditions
- HER2+ Advanced Breast Cancer, Other Solid Tumors
- Being tested
- Chimeric receptor T-cells + Trastuzumab, Fludarabine and Cyclophosphosphamide
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Chimeric receptor T-cells + TrastuzumabDrug
Chimeric receptor T-cells will be administered by infusion. Trastuzumab will be administered intravenously.
Fludarabine and CyclophosphosphamideDrug
Also called Lymphodepletion
3-day chemotherapy regimen of fludarabine and cyclophosphamide for lymphodepletion
| Study group | Role | What they receive |
|---|---|---|
| Chimeric Receptor T-cells | Experimental | Eligible patients will undergo apheresis prior to cycle 1 therapy. Treatment comprises of trastuzumab followed by chimeric receptor T-cells in cycle 1.
During Cycle 2 onwards till disease progression, patients will receive IV or SC trastuzumab only, every 3 weeks. Receives: Drug: Chimeric receptor T-cells + Trastuzumab; Drug: Fludarabine and Cyclophosphosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to treatment failure
defined as the time from the date of study enrolment to the date of the first of the following events: early discontinuation of study therapy, progressive disease, or death due to any cause. Time to treatment failure will be censored at the date of the last follow-up visit for patients who did not discontinue early, who are still alive, and who have not progressed.
Measured: 3 years
Progression-free survival
is defined as the time from the date of study enrolment to the first date of documented disease progression. Progression-free survival will be censored at the date of death for patients who have not had documented disease progression. For patients who are still alive at the time of analysis and who have not had documented disease progression, progression-free survival will be censored at the date of the last follow-up visit.
Measured: 3 Years
Duration of tumour response
Among tumor responders, the duration of tumor response is measured from the date of enrolment until the first date of documented disease progression or death due to any cause, whichever occurs first. Duration of tumor response will be censored at the date of the last follow-up visit for tumor responders who are still alive and who have not progressed.
Measured: 3 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2023
- Study start1 Nov 2026 (estimated)
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HER2+ Advanced Breast CancerStudies of the same condition, open and under way.
- More trials run by National University Hospital, SingaporeThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- This is a single arm, open-label, phase Ib safety lead in, followed by phase II study. The phase Ib segment will be carried out in a standard 3+3 dose escalation design. In the phase II, dose expansion will be carried out to a total of 10 patients at recommended phase II dose in both phase Ib and II. Phase Ib: Patients with advanced solid tumors will be enrolled in a 3+3 dose escalation fashion, with projected enrolment of between 6-30 patients to determine RP2D. Once the RP2D is confirmed, the study will proceed to phase II. Phase II: Up to a total of 10 patients with HER2+ advanced breast cancer will be enrolled. For patients who are in Dose level 3 - 5 will require additional Trastuzumab,erythropoietin beta and Lymphodepletion.
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National University Hospital, Singapore
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Soo Chin Lee, Principal investigator, National University Hospital, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06027983
- Sponsor's protocol ID
- ACEHER2
- Status last verified
- Aug 2025
- First submitted
- 31 Aug 2023
- Last updated
- 23 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lee SC, Shimasaki N, Lim JSJ, Wong A, Yadav K, Yong WP, Tan LK, Koh LP, Poon MLM, Tan SH, Ow SGW, Bharwani L, Yap YS, Foo MZQ, Coustan-Smith E, Sundar R, Tan HL, Chong WQ, Kumarakulasinghe NB, Lieow JLM, Koe PJX, Goh BC, Campana D. Phase I Trial of Expanded, Activated Autologous NK-cell Infusions with Trastuzumab in Patients with HER2-positive Cancers. Clin Cancer Res. 2020 Sep 1;26(17):4494-4502. doi: 10.1158/1078-0432.CCR-20-0768. Epub 2020 Jun 10.
PubMed 32522887
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase IB Followed by Phase II Study of Trastuzumab Combined With Autologous Chimeric Receptor T Cells in HER2+ Advanced Breast Cancer and Other Solid Tumors
- ClinicalTrials.gov ID
- NCT06027983
- Acronym / sponsor ID
- ACEHER2
- Conditions
- HER2+ Advanced Breast Cancer, Other Solid Tumors
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- National University Hospital, SingaporeUniversity, hospital or other
- Study start
- 1 Nov 2026 (estimated)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 7 Sep 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase Ib study aims to assess the safety and feasibility of combination of chimeric receptor T cells with trastuzumab in patients with HER2+ solid tumors, with further expansion of study population in HER2+ metastatic breast cancer once safety has been established.
Detailed description
Hypothesis
Investigators hypothesize that trastuzumab-mediated cytotoxicity will be augmented by the infusion of autologous chimeric receptor T-cells.
Primary Objectives
- To determine the safety of autologous chimeric receptor T-cells in patients with HER2+ advanced solid tumors
- To determine the clinical benefit rate (CBR) of autologous chimeric receptor T-cells in patients with HER2+ advanced breast cancer
Secondary Objectives
- To determine the expansion and persistence of autologous chimeric receptor T-cells after a single infusion in patients with advanced solid tumors
- To determine anti-tumor efficacy in terms of objective response rate (ORR) and progression-free survival (PFS) of autologous chimeric receptor T-cells in patients with HER2+ advanced breast cancer
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a single arm, open-label, phase Ib safety lead in, followed by phase II study. The phase Ib segment will be carried out in a standard 3+3 dose escalation design. In the phase II, dose expansion will be carried out to a total of 10 patients at recommended phase II dose in both phase Ib and II. Phase Ib: Patients with advanced solid tumors will be enrolled in a 3+3 dose escalation fashion, with projected enrolment of between 6-30 patients to determine RP2D. Once the RP2D is confirmed, the study will proceed to phase II. Phase II: Up to a total of 10 patients with HER2+ advanced breast cancer will be enrolled. For patients who are in Dose level 3 - 5 will require additional Trastuzumab,erythropoietin beta and Lymphodepletion.
| Arm | Type | Receives |
|---|---|---|
| Chimeric Receptor T-cells | Experimental | Drug: Chimeric receptor T-cells + Trastuzumab, Drug: Fludarabine and CyclophosphosphamideEligible patients will undergo apheresis prior to cycle 1 therapy. Treatment comprises of trastuzumab followed by chimeric receptor T-cells in cycle 1. During Cycle 2 onwards till disease progression, patients will receive IV or SC trastuzumab only, every 3 weeks. |
Who may qualify
- Ages
- 21 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Age ≥ 21 years.
- Histologically confirmed diagnosis of HER2-positive cancer defined by immunohistochemistry (IHC) to be HER2 IHC3+ or HER2 IHC2+ and FISH positive. If immunohistochemistry is not available, FISH method is acceptable. The HER2 positivities by FISH is determined as FISH amplification ratio positive by institutional guidelines. Tumor subtype for each phase include :
- Phase I: HER2-positive breast or gastric cancer or other treatment-refractory HER2-positive solid tumors
- Phase II : HER2-positive breast carcinoma
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
Key exclusion criteria (16 listed)
- Treatment within the last 30 days with any investigational drug.
- Concurrent administration of any other tumour therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy.
- Major surgery within 28 days of study drug administration.
- Active infection that in the opinion of the investigator would compromise the patient's ability to tolerate therapy.
- Pregnancy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Chimeric receptor T-cells + TrastuzumabChimeric receptor T-cells will be administered by infusion. Trastuzumab will be administered intravenously. | Drug | Chimeric Receptor T-cells |
| Fludarabine and CyclophosphosphamideAlso: Lymphodepletion3-day chemotherapy regimen of fludarabine and cyclophosphamide for lymphodepletion | Drug | Chimeric Receptor T-cells |
Primary outcome
Time to treatment failure
Time frame: 3 years
defined as the time from the date of study enrolment to the date of the first of the following events: early discontinuation of study therapy, progressive disease, or death due to any cause. Time to treatment failure will be censored at the date of the last follow-up visit for patients who did not discontinue early, who are still alive, and who have not progressed.
Progression-free survival
Time frame: 3 Years
is defined as the time from the date of study enrolment to the first date of documented disease progression. Progression-free survival will be censored at the date of death for patients who have not had documented disease progression. For patients who are still alive at the time of analysis and who have not had documented disease progression, progression-free survival will be censored at the date of the last follow-up visit.
Duration of tumour response
Time frame: 3 Years
Among tumor responders, the duration of tumor response is measured from the date of enrolment until the first date of documented disease progression or death due to any cause, whichever occurs first. Duration of tumor response will be censored at the date of the last follow-up visit for tumor responders who are still alive and who have not progressed.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2025.
- Results publication: PubMed 32522887Lee SC, Shimasaki N, Lim JSJ, Wong A, Yadav K, Yong WP, Tan LK, Koh LP, Poon MLM, Tan SH, Ow SGW, Bharwani L, Yap YS, Foo MZQ, Coustan-Smith E, Sundar R, Tan HL, Chong WQ, Kumarakulasinghe NB, Lieow JLM, Koe PJX, Goh BC, Campana D. Phase I Trial of Expanded, Activated Autologous NK-cell Infusions with Trastuzumab in Patients with HER2-positive Cancers. Clin Cancer Res. 2020 Sep 1;26(17):4494-4502. doi: 10.1158/1078-0432.CCR-20-0768. Epub 2020 Jun 10.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Soo Chin Lee principal investigator
National University Hospital, Singapore
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Chimeric receptor T-cells + Trastuzumab and Fludarabine and Cyclophosphosphamide in people with HER2+ Advanced Breast Cancer and Other Solid Tumors, run by National University Hospital, Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 23 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Soo Chin Lee (+65 6908 2222, soo_chin_lee@nuhs.edu.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to treatment failure (time frame: 3 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06027983, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2025.